Background: Depression and heart diseases are very common in general population and they are often associated. Depression is associated with an increased risk of cardiac events and it is known to increase the cost of patient care and to decrease the quality of life. Search method: We systematically reviewed the MEDLINE database for relevant articles and studies. This literature review showed that there are several plausible pathways which could link depression with cardiac diseases, such as epidemiological, genetic, and behavioral factors, inflammation and autonomic nervous system involvement as well as therapeutic interraction. Heart disease and depression have common clinical symptoms such as insomnia, fatigue and impairments in the quality of life that physicians need to better understand and treat. Conclusion: This review revealed evidence that major depressive disorder has a negative influence on mortality in patients with cardiovascular diseases. Further research is needed to achieve more stable and reliable information on the impact of major depressive disorder on mortality in patients with cardiovascular disease, thus, leading to the development of optimal prevention programs.